圖片說(shuō)明：如果能夠及早發(fā)現(xiàn),，結(jié)直腸癌比較容易治療。
（圖片來(lái)源：Punchstock）
英國(guó)科學(xué)家近日發(fā)現(xiàn)一種特殊的基因變異,，它能夠使白種人患結(jié)腸癌（世界第三大癌癥形式）的風(fēng)險(xiǎn)增加10%,，而對(duì)日本人卻毫無(wú)影響。這是首個(gè)具種族特異性的與結(jié)腸癌易感性有關(guān)的基因變異,，有望幫助人們開(kāi)展特定種族的結(jié)直腸癌風(fēng)險(xiǎn)評(píng)估,，以便做到早發(fā)現(xiàn)早治療。相關(guān)論文3月30日在線發(fā)表于《自然—遺傳學(xué)》（Nature Genetics）上,。

領(lǐng)導(dǎo)此次研究的是英國(guó)愛(ài)丁堡大學(xué)的Malcolm Dunlop,。研究人員從1000多個(gè)蘇格蘭癌癥病人身上采集DNA樣本,，篩選與癌癥有關(guān)的基因變異,。隨后，他們?cè)诹硗鈳浊€(gè)病人身上重復(fù)這一過(guò)程,，并與來(lái)自其它種族的樣本進(jìn)行比較,。結(jié)果在基因組中發(fā)現(xiàn)了三個(gè)與結(jié)直腸癌存在明確關(guān)聯(lián)的變異，其中一個(gè)位于11號(hào)染色體上的變異能夠增加蘇格蘭人的結(jié)腸癌易感性,，而對(duì)日本人卻沒(méi)有影響,。

Dunlop表示，這種種族間差別的存在原因目前尚不清楚,，或許可以歸因于種族間其它未知的遺傳差異，或是飲食等生活方式的差別,。

令人感興趣的是,，這一基因變異只在影響結(jié)腸癌風(fēng)險(xiǎn)方面具有種族特異性。研究發(fā)現(xiàn),，帶有這一變異的白種人和日本人在患直腸癌的風(fēng)險(xiǎn)方面大略相當(dāng),，表明這一變異的作用精細(xì)而具有特異性。

在3月30日在線發(fā)表的另一項(xiàng)類(lèi)似研究中,，由英國(guó)薩頓癌癥研究所的Richard Houlston領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn)了另外兩個(gè)與結(jié)直腸癌有關(guān)的基因變異,。Dunlop說(shuō)，帶有全部這幾個(gè)變異的人患結(jié)直腸癌的風(fēng)險(xiǎn)是不帶這些變異人的4到5倍,。

英國(guó)目前已經(jīng)開(kāi)始一個(gè)全國(guó)性的結(jié)直腸癌排查項(xiàng)目,。Dunlop認(rèn)為，在患病前就檢測(cè)出危險(xiǎn)基因?qū)妬?lái)說(shuō)具有重要的意義,，它將允許人們“修剪”自己的生活方式以盡力避免患上腸道癌癥,。

他同時(shí)表示,，雖然還需要一定的時(shí)間，但具種族特異性的,、甚至是個(gè)體化的癌癥易感性測(cè)試必將成為現(xiàn)實(shí),。（科學(xué)網(wǎng) 梅進(jìn)/編譯）

生物谷推薦原始出處：

（Nature Genetics），doi:10.1038/ng.133,，Albert Tenesa,，Malcolm G Dunlop

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21
Albert Tenesa1,31, Susan M Farrington1,31, James G D Prendergast1, Mary E Porteous2, Marion Walker1, Naila Haq1, Rebecca A Barnetson1, Evropi Theodoratou1,3, Roseanne Cetnarskyj2, Nicola Cartwright1, Colin Semple1, Andrew J Clark1, Fiona J L Reid4, Lorna A Smith4, Kostas Kavoussanakis4, Thibaud Koessler5, Paul D P Pharoah5, Stephan Buch6,7, Clemens Schafmayer7,8, Jürgen Tepel6,8, Stefan Schreiber7,9, Henry Völzke10, Carsten O Schmidt10, Jochen Hampe6, Jenny Chang-Claude11, Michael Hoffmeister12, Hermann Brenner12, Stefan Wilkening13, Federico Canzian13, Gabriel Capella14, Victor Moreno15, Ian J Deary16, John M Starr17, Ian P M Tomlinson18, Zoe Kemp18, Luis Carvajal-Carmona18, Emily Webb19, Peter Broderick19, Jayaram Vijayakrishnan19, Richard S Houlston19, Gad Rennert20, Dennis Ballinger21, Laura Rozek22, Stephen B Gruber22, Koichi Matsuda23, Tomohide Kidokoro23, Yusuke Nakamura23, Brent W Zanke24,25,26, Celia M T Greenwood24,27,28, Jagadish Rangrej18,27, Rafal Kustra24, Alexandre Montpetit29, Thomas J Hudson24,25, Steven Gallinger24,30, Harry Campbell1,3 & Malcolm G Dunlop1

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8  10-10), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6  10-26) and 18q21 (rs4939827; OR = 1.2; P = 7.8  10-28). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology.

（Nature Genetics），doi:10.1038/ng.111,，Ian PM Tomlinson,，Richard S Houlston

A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3
Ian PM Tomlinson1,38, Emily Webb2, Luis Carvajal-Carmona1, Peter Broderick2, Kimberley Howarth1, Alan M Pittman2, Sarah Spain1, Steven Lubbe2, Axel Walther1, Kate Sullivan2, Emma Jaeger1, Sarah Fielding2, Andrew Rowan1, Jayaram Vijayakrishnan2, Enric Domingo1, Ian Chandler2, Zoe Kemp1, Mobshra Qureshi2, Susan M Farrington3, Albert Tenesa3, James GD Prendergast3, Rebecca A Barnetson3, Steven Penegar2, Ella Barclay1, Wendy Wood2, Lynn Martin1,4,5, Maggie Gorman1, Huw Thomas6, Julian Peto7,8, D Timothy Bishop9, Richard Gray10, Eamonn R Maher5, Anneke Lucassen11, David Kerr12, D Gareth R Evans4, The CORGI Consortium37, Clemens Schafmayer13,14, Stephan Buch16,17, Henry Völzke15, Jochen Hampe16, Stefan Schreiber14,17, Ulrich John15, Thibaud Koessler18, Paul Pharoah18, Tom van Wezel19, Hans Morreau19, Juul T Wijnen20, John L Hopper21, Melissa C Southey22, Graham G Giles21,23, Gianluca Severi23, Sergi Castellví-Bel24, Clara Ruiz-Ponte25, Angel Carracedo25, Antoni Castells24, The EPICOLON Consortium37, Asta Försti26,27, Kari Hemminki26,27, Pavel Vodicka28, Alessio Naccarati28, Lara Lipton29, Judy WC Ho30, K K Cheng30, Pak C Sham30, J Luk30, Jose AG Agúndez31, Jose M Ladero32, Miguel de la Hoya33, Trinidad Caldés33, Iina Niittymäki34, Sari Tuupanene34, Auli Karhu34, Lauri Aaltonen34, Jean-Baptiste Cazier35, Harry Campbell36,38, Malcolm G Dunlop3,38 & Richard S Houlston2,38

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10-4 in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5  10-13 overall; P = 6.9  10-12 replication), and rs16892766, at 8q23.3 (P = 3.3  10-18 overall; P = 9.6  10-17 replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.